A Review of the Toxicity of HIV Medications II: Interactions with Drugs and Complementary and Alternative Medicine Products

Abstract

For many patients today, HIV has become a chronic disease. For those patients who have access to and adhere to lifelong antiretroviral (ARV) therapy, the potential for drugdrug interactions has become a real and life-threatening concern. It is known that most ARV drug interactions occur through the cytochrome P450 (CYP) pathway. Medications for comorbid medical conditions, holistic supplements, and illicit drugs can be affected by CYP inhibitors and inducers and have the potential to cause harm and toxicity. Protease inhibitors (PIs) tend to inhibit CYP3A4, while most nonnucleoside reverse transcriptase inhibitors (NNRTIs) tend to induce the enzyme. As such, failure to adjust the dose of coadministered medications, such as statins and steroids, may lead to serious complications including rhabdomyolysis and hypercortisolism, respectively. Similarly, gastric acid blockers can decrease several ARV absorption, and warfarin doses may need to be adjusted to maintain therapeutic concentrations. Illicit drugs such as methylenedioxymethamphetamine (MDMA, "ecstasy") in combination with PIs lead to increased toxicity, while the concomitant administration of sedative drugs such as midazolam and alprazolam in patients taking PIs can result in prolonged sedation, delayed recovery, and increased length of stay. Even supplements like St. John's Wort can alter PI concentrations. In theory, any drug that is metabolized by CYP has potential for a pharmacokinetic drug-drug interaction with all PIs, cobicistat, and most NNRTIs. When adding a new medication to an ARV regimen, use of a drug-drug interaction software and/or consultation with a clinical pharmacist/pharmacologist or HIV specialist is recommended.

Rilpivirine and Doravirine Have Complementary Efficacies Against NNRTI-Resistant HIV-1 Mutants

“…If the NNRTIs are carefully chosen, it should be difficult for the virus to develop resistance, and the low toxicity of the NNRTIs would be an advantage for patients [26, 27]. Whether DOR and RPV represent a clinically useful pair of NNRTIs that could be used together in cART remains to be seen; however, it would be useful to find additional pairs of NNRTIs whose resistance profiles do not overlap.…”

Prevalence and Characteristics of CAM Use among People Living with HIV and AIDS in Lebanon: Implications for Patient Care

“…For example, there is some evidence that of an association of Echinacea with increased HIV viral load [57] and of Kava with hepatotoxicity [58]. Furthermore, garlic [59], vitamin C [60], and St John's wort [61–63] may decrease the efficacy of HAART. Aloe may reduce HAART drug absorption, and Ginkgo, Ginseng, and milk thistle may intensify HAART-related side effects [52].…”

Addressing Antiretroviral Therapy‐Associated Drug‐Drug Interactions in Patients Requiring Treatment for Opportunistic Infections in Low‐Income and Resource‐Limited Settings

“…Clinically significant DDIs occur frequently in HIV‐infected patients treated with ART, with an increased incidence among the elderly, those with multiple comorbid conditions, those receiving complex regimens, and those living in low‐income or resource‐limited settings . The majority of DDIs are the result of ART metabolism via the cytochrome P450 (CYP) system, particularly CYP3A, CYP2D6, CYP2C9/19, and CYP2B6, but may also be mediated through drug transporters such as organic anion transporting polypeptide or elimination mechanisms including p‐glycoprotein (PGP) …”